Ординатура / Офтальмология / Английские материалы / Clinical Pathways in Glaucoma_Zimmerman, Kooner_2001
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150 Glaucoma Associated with Inflammation
primary candidates for use of the CsA.25 Further studies will evaluate the use of topical CsA in the treatment of herpetic keratitis associated with glaucoma.
GLAUCOMA ASSOCIATED WITH EPISCLERITIS
Definition
How Is Glaucoma Associated with Episcleritis Defined?
Intraocular pressure elevation is not seen frequently with episcleritis. Similar to all inflammatory conditions, elevated IOP does not always cause optic nerve damage and visual field loss, and does not always need to be lowered with IOP-lowering agents. After observation and/or treatment, the underlying inflammatory condition usually resolves, and the IOP typically returns to normal level without damaging the optic nerve.
Epidemiology and Importance
How Often Does Episcleritis Present with Elevated IOP?
Episcleritis is rarely associated with elevated IOP.26,27 Few cases have been reported in the literature.28,29 Glaucoma was found in 9% (9 out of 100) of the eyes with episcleritis in a recent retrospective study of patients with episcleritis, and none of the patients had a history of glaucoma.30 Four of those nine patients were using topical steroids for recurrent episcleritis of the initial exam. Glaucoma was more common in patients with recurrent episcleritis but was infrequent with bilateral involvement.30 Possible elevation of the episcleral venous pressure does not seem to influence the IOP, but this is still controversial.26,28,31
Diagnosis and Differential Diagnosis
How Does Episcleritis Present?
Episcleritis is a benign condition that presents with acute onset of redness, mild discomfort, and infrequently mild pain. It is often recurrent and is bilateral in every third patient with episcleritis. It occurs in young adults32 and appears to be twice as common in females.30 Visual acuity is usually not affected; the redness is commonly limited to a scleral sector, but occasionally can be diffuse. Conjunctival and episcleral vessels are engorged and can be moved over the sclera. The cornea is usually clear, and the anterior chamber is quiet.32,33 Episcleritis is mostly idiopathic; however, an associated systemic disease is found in a third of the cases,26,30,32 the most common being atopy.30 Rosacea can also cause episcleritis.
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What Is the Differential Diagnosis of Glaucoma
Associated with Episcleritis?
Inflammation of the sclera and episclera may be associated with systemic diseases. Sainz et al29 evaluated ocular complications and specific systemic disease association in 266 patients (358 eyes) with different types of scleritis and episcleritis; 37% of patients with scleritis developed decrease in vision, 42% had an associated anterior uveitis, 14% developed peripheral ulcerative keratitis, 13% developed glaucoma, 17% formed cataracts, and 6% had fundus abnormalities. More than half of the patients (57%) had an associated disease. These findings were more typical for necrotizing scleritis. In contrast, only 2% of patients with simple and nodular episcleritis developed some degree of visual loss, 11% had an associated anterior uveitis, 4% developed glaucoma, and 2% formed cataracts. Every third patient had a specific disease association.29
Treatment and Management
How Is Episcleritis Treated?
Treatment of episcleritis is directed at the underlying cause if one is identified (i.e., elimination of irritants and application of mast cell stabilizers for atopy, doxycycline for rosacea).30 Because episcleritis is a self-limited condition, nonspecific treatment is not necessary if the patient is asymptomatic. Idiopathic symptomatic episcleritis can be treated with cold compresses, iced artificial tears,30 and topical vasoconstrictors. Treatment of episcleritis with topical flurbiprofen has not been shown to be more effective than placebo.34 Treatment of recurrent episcleritis with low-dose oral nonsteroidal antiinflammatory drugs (NSAIDs) is effective30 and has not been associated with IOP elevation.
Topical treatment with the relatively new NSAID aminothiazole hydrochloride 0.1%35,36 was effective in reducing inflammation in mild episcleritis within the first week of administration of the drug. It was not effective against severe episcleritis. There was no effect on IOP.37
How Is Glaucoma Associated with Episcleritis Managed?
There are different mechanisms for elevated IOP in a patient with episcleritis. Each condition is managed accordingly.
How Is Steroid-Induced Elevation of IOP Managed?
Corticosteroids are always effective in reducing the symptoms of episcleritis,34,38,39 but IOP should be monitored weekly and therapy with steroids should not be continued longer than a few weeks30,32 (see also Chapter 15).
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How Is Elevated IOP with Open Anterior Chamber
Angle Managed?
There are almost no reported causes in the literature of an association of episcleritis with IOP elevation. Watson40 did not find any evidence of glaucoma in 192 eyes of 117 patients with episcleritis. Harbin and Pollack28 described two patients with episcleritis and IOP elevation. One of the four eyes had anterior uveitis. The authors assume that in the other 3 eyes the inflammation was limited to the angle structures, especially the trabecular meshwork, causing impairment of the aqueous outflow without involving the iris and ciliary body vasculature. The low facility of outflow implies that the increased episcleral venous pressure was not the mechanism of IOP elevation. These patients respond to aqueous suppressants and treatment with topical steroids.28
How Is Elevated IOP Associated with Angle Closure Managed?
Acute angle closure is a rare complication of episcleritis. These eyes should respond to standard therapy for acute angle closure with neodymium:yttrium- aluminum-garnet (Nd:YAG) laser iridotomy or peripheral iridectomy41 (see also Chapter 5).
How Is Preexisting Open-Angle Glaucoma Associated with Episcleritis Managed?
Patients with preexisting open-angle glaucoma have a higher chance of being steroid responders and should therefore be monitored closely when treated with topical steroids.42 Among comparable age groups, the steroid-induced IOP elevation was always greater in glaucomatous than in normal eyes.43
Future Considerations
The development of soft steroids that will treat inflammation without elevation of IOP will greatly aid in the management of episcleritis. Recent arrivals in this group are loteprednol and rimexolone.
GLAUCOMA ASSOCIATED WITH SCLERITIS
Definition
How Is Glaucoma Associated with Scleritis Defined?
As in all inflammatory conditions associated with IOP elevation, glaucoma associated with scleritis must meet the criteria of glaucomatous damage: glaucomatous optic nerve, visual field loss, and IOP elevation developing secondary to scleritis.
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How Does Scleritis Present?
Scleritis is a serious and damaging ocular condition. It usually presents with severe pain, radiating to the orbit, forehead, cheekbone, and teeth. The patient complains of photophobia and insidious decrease of vision. The eye is red due to injection of scleral, episcleral, and conjunctival vessels. The sclera may be affected only in one sector or diffusely. As opposed to episcleral vessels, the affected scleral vessels cannot be moved with a cotton swab. The scleritis can be recurrent and is associated with a systemic disease in approximately 50% of cases. It can be divided into anterior and posterior scleritis.32,44
Epidemiology and Importance
How Often Is Scleritis Associated with Elevated IOP?
Most studies have found that 12% to 13% of patients with anterior scleritis present with glaucoma;29,32,41 20% of those eyes may also have associated keratitis.26 Elevated IOP was detected in 18.7% of eyes with rheumatoid scleritis.27 However, 50% of eyes enucleated for scleritis also had glaucomatous optic neuropathy.41 Episcleritis normally does not progress to scleritis, except in the case of herpes zoster, which may start as an episcleritis and reappear 3 months later as a scleritis at the same site.26
Wilhelmus et al45 reviewed 92 enucleated eyes with histopathologic evidence of scleral inflammation. They also examined 114 eyes from 81 patients with scleritis. Almost half of the enucleated eyes and every fifth eye in examined patients showed evidence of increased IOP, the most common causes of which were damage to the trabecular meshwork from iridocyclitis, overlying corneoscleral inflammation, or peripheral anterior synechiae. Other causes included topical corticosteroid use; angle neovascularization in enucleated, but not in clinically observed, eyes; and posterior scleritis with secondary angle closure.
Sainz and co-workers46 found that in 42% of patients with scleritis, inflammation may extend to the anterior uveal tract and cause anterior uveitis, with consequent development of glaucoma in 19% of eyes in that group.46 Posterior scleritis is typically not associated with glaucoma, but angle closure secondary to choroidal effusion has been reported in the literature.45–51 In 5% of patients with scleritis, the elevated IOP can be related to the administration of corticosteroids used to treat the underlying condition.
Why Is the Intraocular Pressure Elevated in Scleritis?
There are several mechanisms for raised pressure in patients with scleritis. These patients may present with any of the following four clinical features:
ELEVATION OF IOP WITH OPEN ANTERIOR CHAMBER ANGLE
The IOP may be elevated in the presence of an open anterior chamber angle. This may be caused by (1) increased resistance to outflow from inflammation in
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the trabecular meshwork;45 (2) preexistent abnormalities in outflow pathways that are impaired by perilimbal inflammation and edema; (3) abnormal steroid response;45,52 and (4) elevated episcleral venous pressure.53
Acute uveitis causing damage to the trabecular meshwork and occlusion of the trabecular meshwork by inflammatory cells was the main mechanism of IOP elevation in pathologic studies of the eyes with glaucoma and scleritis.45 Discontinuation of steroids decreased IOP in the eyes with induced ocular hypertension due to abnormal steroid response.
Wilhelmus and associates45 reported that 4 out of 92 eyes enucleated for scleritis had an open angle and did not demonstrate any trabecular meshwork abnormalities. They were thought to have primary open-angle glaucoma. All these eyes had lymphocytic cuffing around the intrascleral outflow channels with perivasculitis of the anterior uvea, which may have caused increased resistance to aqueous flow. The possible increase of the episcleral venous pressure has been argued as a cause of the elevated IOP.45
ELEVATION OF IOP ASSOCIATED WITH ANGLE CLOSURE
Angle closure secondary to peripheral anterior synechiae may cause elevated IOP. However, this is unlikely to occur in scleritis without concurrent uveitis.45 Acute angle closure may occur in eyes with posterior scleritis secondary to choroidal effusion and forward rotation of the iris-ciliary body.47–51
PUPILLARY BLOCK SECONDARY TO POSTERIOR SYNECHIAE
Concurrent uveitis may cause formation of posterior synechiae with seclusio pupillae and iris bombé.
NEOVASCULAR GLAUCOMA
Neovascular glaucoma can occur in eyes affected by scleritis. In a series of 92 eyes enucleated for scleritis, 14 eyes (15%) had a neovascular membrane covering the anterior chamber angle.45
Diagnosis and Differential Diagnosis
How Is Glaucoma Secondary to Scleritis Diagnosed?
Typically, the diagnosis is based on clinical examination.26 In addition to routine laboratory blood tests, skin tests, radiologic tests, electrodiagnostic tests, and tissue biopsy for uveitis workup, patients should have documented damage to the optic nerve secondary to the IOP elevation from scleritis.
What Is the Differential Diagnosis of Glaucoma
Associated with Scleritis?
The differential diagnosis of scleritis is crucial for early and effective treatment. The recognition of necrotizing scleritis is particularly important because it is
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frequently associated with ocular complications and a bad ocular prognosis. Scleritis associated systemic vasculitis indicates its generalization with potential development of lethal systemic complications. Only the early diagnosis and an adequate aggressive therapy can preserve ocular functions and the patient’s life. Conventional steroid therapy generally fails to control the inflammatory activity in necrotizing scleritis. However, application of nonsteroidal immunosuppressive drugs has been shown to control the vasculitic conditions in the majority of cases, to improve ocular prognosis, and to reduce mortality.54 The dry eye syndrome secondary to Sjögren’s syndrome or medication use must be differentiated and treated appropriately to avert sightthreatening complications and to alleviate substantial discomfort.55
Acute rheumatic fever in a young child with fever, sore throat, joint pains, and malaise can present together with scleritis, uveitis, and glaucoma. Patients may have an increased antistreptolysin-O antibody titer. Testing for antistreptococcal antibody is indicated in diagnosing rheumatic fever complicated with scleritis, uveitis, and glaucoma.56
Treatment and Management
Treatment of glaucoma secondary to scleritis is often difficult and complicated. It usually includes topical and systemic corticosteroids and NSAIDs. Aqueous suppressants are applied to lower the IOP. Discontinuation of steroids that are used to treat the underlying scleritis is not always feasible even if an abnormal steroid response is suspected. If medical therapy completely fails to control the IOP, trabeculectomy or implantation of a drainage device may be necessary.
Acute angle closure can be treated with standard therapy regimen (see also Chapter 5). Formation of posterior synechiae can be prevented with the use of mydriatics. Iris bombé is treated initially with mydriatics. If this is unsuccessful, laser pupilloplasty can be tried, or a peripheral iridotomy/iridectomy can be placed.
Future Considerations
Identification and description of inflammatory mechanisms will be necessary for the development of new medications that will control intraocular inflammation without affecting the IOP.
GLAUCOMA ASSOCIATED WITH UVEITIS
Definition
What Is Uveitic Glaucoma?
Glaucoma can be called uveitic glaucoma only when the glaucomatous optic nerve damage, glaucomatous visual field defects, and IOP elevation associated with uveitis have been documented. More specific terms such as hypertensive uveitis can be used for conditions not meeting all the aforementioned criteria.57
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What Is the Etiology of Glaucoma Associated with Uveitis?
Elevated IOP commonly complicates any type of uveitis. The inflammatory cells and mediators, as well as the corticosteroids used in the treatment of the uveitis, all contribute to the pathogenesis of uveitic glaucoma by altering the anatomy of the anterior chamber and its angle and by influencing aqueous production and outflow. These changes disrupt the homeostasis of IOP control. Changes in the angle can be acute, such as in secondary angle closure with pupillary block glaucoma, or chronic, such as combined steroid-induced and secondary open-angle glaucoma.57
Uveitic glaucoma may occur by acute angle closure due to iris bombé caused by posterior synechiae, chronic angle closure due to peripheral anterior synechiae, open-angle glaucoma due to obstruction and/or inflammation of the trabecular meshwork, or any combination of the above. If secretory hypotony develops, it may mask compromised outflow. Corticosteroids for treatment of the uveitis may cause an elevation of IOP. Thorough differential diagnosis of the pathophysiologic mechanisms involved in uveitic glaucoma is absolutely essential for successful management of these conditions.58 In uveitic glaucoma the optic neuropathy is caused by an increased IOP, which by itself is elevated due to complications caused by inflammation of the uvea. In addition, inflammatory conditions, such as sarcoidosis, can cause direct damage to the optic nerve.59
Does Uveitis in a Glaucomatous Eye Always Mean
Uveitic Glaucoma?
No, even though the differentiation between uveitic glaucoma and glaucoma with uveitis can be difficult, it is important to consider angle closure or openangle glaucoma and its subtypes in the differential diagnosis of uveitic glaucoma. Pseudoexfoliation, neovascularization, and laser or intraocular surgery may cause secondary inflammation due to disturbance of the blood–aqueous barrier.
Epidemiology and Importance
How Common Is Uveitic Glaucoma?
The epidemiology of uveitic glaucoma is difficult to define because different investigators define glaucoma and uveitis differently in their studies. The frequency of glaucoma in uveitis differs among the different uveitis entities. Anterior uveitis represents 2760 to 45%61 of all uveitis syndromes, achieving 0.2 to 0.4% lifetime cumulative incidence in the general population.62 Human leukocyte antigen HLA-B27–positive acute anterior uveitis is associated with a more serious prognosis when compared to HLA-B27–negative acute anterior uveitis.63
Panek and associates64 noted that 20 out of 76 patients with chronic uveitis developed secondary glaucoma, and among 24 patients with acute uveitis secondary glaucoma was found in three patients. The authors concluded that their results confirmed the concept that secondary glaucoma is a management problem in patients with chronic rather than acute uveitis. In another study, out of 340 children with anterior uveitis 46 (13.5%) developed secondary glaucoma.65
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Is the Elevated IOP More Often Associated with a Closed or Open Anterior Chamber Angle?
The elevated IOP in eyes with uveitis is more often associated with open anterior chamber angles than with angle closure. Frequently the elevated IOP is caused by clogging of the trabecular meshwork with inflammatory cells without developing peripheral anterior synechiae, and rarely by precipitates on the trabecular meshwork without signs of inflammation.66,67 IOP elevation may be caused by obstruction of aqueous outflow by serum components,68 or swelling of the stroma,69 or inflammation of the endothelium of the trabecular meshwork. Glaucoma commonly complicates herpetic uveitis by causing trabeculitis with obstruction of the trabecular meshwork with inflammatory cells.6,70,71 However, closed anterior chamber angles can also be encountered. Several mechanisms of angle closure are possible:
PRIMARY ANGLE CLOSURE
Primary angle closure occurs primarily in predisposed eyes with narrow angles. It is usually difficult to establish what is the primary event.
SECONDARY ANGLE CLOSURE
Peripheral Anterior Synechiae
Inflammatory cells accumulating in the drainage angle of the anterior chamber adhere to the trabecular meshwork and peripheral iris causing peripheral anterior synechiae (PAS). Iris neovascularization that may develop from chronic inflammation can also contribute to the formation of PAS. This leads to occlusion of the drainage angle and thus elevation of the IOP.
Forward Rotation of the Ciliary Body
Edema of the ciliary body may rotate the lens-iris diaphragm forward. The anterior chamber becomes shallow and the angle closes.49
Pupillary Block and Posterior Synechiae
Formation of inflammatory adhesions between the iris sphincter and the lens, or the vitreous in the aphakic patient, or the intraocular lens (IOL) in the pseudophakic patient causes the interruption of aqueous flow from the posterior to the anterior chamber.72
Diagnosis and Differential Diagnosis
How Is Glaucoma Associated with Uveitis Diagnosed?
The diagnosis of active inflammation is based on detection of inflammatory cells in the aqueous and/or vitreous. Flare in the anterior chamber is evidence of vascular incompetence and is usually chronic.73 Careful gonioscopy is absolutely essential for making the correct diagnosis. The presence of precipitates on the trabecular meshwork and scattered peripheral anterior synechiae even in the absence of obvious uveitis is a sign of ocular inflammation.66
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What Is the Differential Diagnosis of Glaucoma
Associated with Uveitis?
Adenoma of nonpigmented epithelium of the ciliary body can present as anterior uveitis and glaucoma.74 Uveitis glaucoma hyphema syndrome75,76 together with lens-induced uveitis and phacolytic glaucoma77 should be included in the differential diagnosis.
Severe corneal edema in aphakic eye can develop secondary to neovascular glaucoma.78 Nonpenetrating trauma to the eye can induce nonspecific intracameral inflammation with cells, flare, fibrin, and increased IOP.79
Rarely, inflammatory glaucoma may present with acute onset of IOP elevation and inflammatory precipitates on the trabecular meshwork in otherwise quiet eyes. This condition is called Grant’s syndrome. Ultrasound biomicroscopy can be useful for imaging inflammatory precipitates in the angle. These patients do not respond well to typical IOP lowering agents but have excellent response to topical steroids. This condition is often bilateral and tends to recur. It may have a systemic association with sarcoidosis. Grant’s syndrome should be considered as a possible diagnosis of elevated IOP in clinically quiet eyes.66,67
Treatment and Management
Treatment is simultaneously aimed at the underlying uveitis, preventing future complications that may cause IOP elevation and/or vision loss, and at lowering the IOP if necessary to prevent glaucomatous optic neuropathy. Decreased inflammation in the trabecular meshwork can increase aqueous drainage and thus lower IOP. The reverse, however, might be true if the ciliary body recovers its secretory function with decreasing inflammation. Medical and surgical options are available (Fig. 8–1).
What Is the Medical Therapy?
There are several options for the medical therapy of this condition:
CORTICOSTEROIDS
Corticosteroids are the mainstay of therapy for uveitis. Topical steroids are effective for anterior segment inflammation but not against posterior and intermediate uveitis in the phakic eye. However, they also have the potential to raise the IOP (see also Chapter 15) and cause ocular complications such as fungal keratitis.80
Dexamethasone and prednisolone are the most potent topical corticosteroids available, but have an increased risk of IOP elevation. Fluorometholone and medrysone are weaker steroids, but are less likely to produce IOP elevation. Newer “soft steroids” like loteprednol and rimexolone seem to have the properties to treat ocular inflammation effectively with less risk of affecting the
IOP.81,82
Periocular injections provide effective treatment for posterior and intermediate uveitis. Hydrocortisone subconjunctival injection dosages range from 50 to 125 mg. Methylprednisolone depot is available for subconjunctival injection in
Figure 8–1. Management of uveitic glaucoma. IOP, intraocular pressure.
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